FDA Approval of Companion Diagnostics in Pharmacogenomics

Pharmacogenomics (abbreviated PGx) is the use of genetic information in tailoring or predicting drug response – examples include whether a patient has a particularly favorable genetic profile that indicates that a drug will likely work, or whether the tumor from a cancer patient appears to be genetically vulnerable to chemotherapeutic drugs. In general, the FDA does not regulate the vast field of genetic testing (see here for more background). However, the FDA has been involved in regulating some coupling of genetic testing with the use of FDA-approved drugs (resulting in a companion diagnostic). This paradigm of approving drugs for specific genetically typed populations began with the approval of Herceptin and an accompanying genetic test in 1998. Herceptin is a monoclonal antibody that targets a particular protein on breast cancer cells. The subset of cancer patients who tested for HER-2 positive cancer cells became the target group for the use of this drug. This drug was developed through the detailed molecular study of cancer cells and so the genetic profile for the drug was known at the start. The trend toward the approval of companion diagnostic continues. The FDA definition: "An in vitro companion diagnostic device is an in vitro diagnostic device that provides information that is essential for the safe and effective use of a corresponding therapeutic product. The use of an IVD companion diagnostic device with a particular therapeutic product is stipulated in the instructions for use in the labeling of both the diagnostic device and the corresponding therapeutic product, as well as in the labeling of any generic equivalents and biosimilar equivalents of the therapeutic product." Here is the current FDA list of approvals. The FDA has approved another companion diagnostic for use in the treatment of colon cancer. In this case, the TheraScreen test for mutations in the K-ras gene will be used to evaluate the likelihood that the already approved Erbitux will be effective in the treatment of colon cancer. The infilitration of PGx into drug prescribing does not stop there. Fast forward and we now have dozens of drugs (not all of which are newly developed) which include PGx information on their FDA-approved labels. This reflects the FDA’s increasing embrace of genomic information as a component of the therapeutic information climate, and it continues to advise drug companies who wish to include such information by issuing guidance on how to incorporate a genomic dimension into clinical trials. A number of PGx correlates for drug use have come to light after drug approval, as researchers attempt to identify successes and failures as the drug is used in the general population (see here for earlier story on Plavix and PGx). The PGx field is distinctive in genetic testing as the FDA is taking affirmative steps to manage the use of genetic information in drug prescribing, while it continues to exercise what it describes as “enforcement discretion” with respect to other applications of genetic testing.